Evidence map›Paper›PMID 34965440›Full record

ArticleCell reports2021

Kaposi's sarcoma herpesvirus activates the hypoxia response to usurp HIF2α-dependent translation initiation for replication and oncogenesis.

Omayra Méndez-Solís, Mourad Bendjennat, Julian Naipauer, Phaedra R Theodoridis, J J David Ho, Ramiro E Verdun, Joshua M Hare, Ethel Cesarman, Stephen Lee, Enrique A Mesri

Open access · goldAbstract read
In one paragraph

Article in Cell reports, 2021. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 14 papers.

0numbers the graph read from it
0cells of the map it votes in
14citing papers in PubMed
0.5field-weighted citation impact, top 30% of its field
1 · What the graph read from it

What it found

Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.

The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.

2 · The registry

The trial behind it

Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.

Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.

3 · Its place in the literature

Who cites it

14 citing papers in PubMed, 16 citations in OpenAlex.

  1. Article
  2. Review
  3. Article
  4. Article
  5. Review
  6. Viral oncogenesis in cancer: from mechanisms to therapeutics.Signal transduction and targeted therapy · 2025
    Review
  7. Article
  8. Article
  9. Hypoxia and HIF-1α promote lyticJournal of virology · 2023
    Article
  10. Review
  11. Review
  12. Hypoxia in Skin Cancer: Molecular Basis and Clinical Implications.International journal of molecular sciences · 2023
    Review
  13. Review
  14. Article
4 · The record

Corrections and comments

PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.

5 · Who and what money

Authors and funding

10 authors at 2 institutions in 1 country.

Omayra Méndez-SolísTumor Biology Program, Sylvester Comprehensive Cancer Center, University of Miami Miller School of Medicine, Miami, FL 33136, USA; Miami Center for AIDS Research, Department of Microbiology and Immunology, University of Miami Miller School of Medicine, Miami, FL 33136, USA.
Mourad BendjennatTumor Biology Program, Sylvester Comprehensive Cancer Center, University of Miami Miller School of Medicine, Miami, FL 33136, USA; Miami Center for AIDS Research, Department of Microbiology and Immunology, University of Miami Miller School of Medicine, Miami, FL 33136, USA; Department of Radiation Oncology, University of Miami Miller School of Medicine, Miami, FL 33136, USA.
Julian NaipauerTumor Biology Program, Sylvester Comprehensive Cancer Center, University of Miami Miller School of Medicine, Miami, FL 33136, USA; Miami Center for AIDS Research, Department of Microbiology and Immunology, University of Miami Miller School of Medicine, Miami, FL 33136, USA.
Phaedra R TheodoridisTumor Biology Program, Sylvester Comprehensive Cancer Center, University of Miami Miller School of Medicine, Miami, FL 33136, USA; Department of Biochemistry and Molecular Biology, University of Miami Miller School of Medicine, Miami, FL 33136, USA.
J J David HoTumor Biology Program, Sylvester Comprehensive Cancer Center, University of Miami Miller School of Medicine, Miami, FL 33136, USA; Department of Biochemistry and Molecular Biology, University of Miami Miller School of Medicine, Miami, FL 33136, USA.
Ramiro E VerdunCancer Epigenetics Program, Sylvester Comprehensive Cancer Center, University of Miami Miller School of Medicine, Miami, FL 33136, USA; Department of Medicine, University of Miami Miller School of Medicine, Miami, FL 33136, USA.
Joshua M HareDepartment of Medicine, University of Miami Miller School of Medicine, Miami, FL 33136, USA; Interdisciplinary Stem Cell Institute, University of Miami Miller School of Medicine, Miami, FL 33136, USA.
Ethel CesarmanDepartment of Pathology and Laboratory Medicine, Weill Cornell Medicine, New York, NY 10021, USA.
Stephen LeeTumor Biology Program, Sylvester Comprehensive Cancer Center, University of Miami Miller School of Medicine, Miami, FL 33136, USA; Department of Biochemistry and Molecular Biology, University of Miami Miller School of Medicine, Miami, FL 33136, USA. Electronic address: stephenlee@med.miami.edu.
Enrique A MesriTumor Biology Program, Sylvester Comprehensive Cancer Center, University of Miami Miller School of Medicine, Miami, FL 33136, USA; Miami Center for AIDS Research, Department of Microbiology and Immunology, University of Miami Miller School of Medicine, Miami, FL 33136, USA. Electronic address: emesri@med.miami.edu.
University of Miami · USCornell University · US

Funding

Leadership and Operations Center (LOC), AIDS Clinical Trials Group (ACTG); LOC 1/UM1AI068636 · NIAID · UNIV OF NORTH CAROLINA CHAPEL HILL · PI Joseph J Eron, RAJESH T GANDHI · 2011 to 2026
$1073.1M
Statistical and Data Management Center (SDMC), AIDS Clinical Trials Group (ACTG)UM1AI068634 · NIAID · HARVARD UNIVERSITY D/B/A HARVARD SCHOOL OF PUBLIC HEALTH · PI Marlene Ann Cooper, Michael David Hughes · 2011 to 2026
$246.6M
Validation, CLIA and Qualification (VQC): Enhancing the RS ratio as a tool for AIDS Clinical Trial Group (ACTG) tuberculosis trialsUM1AI106701 · NIAID · UNIVERSITY OF CALIFORNIA LOS ANGELES · PI Grace M Aldrovandi · 2014 to 2026
$116.8M
University of Southern CaliforniaU01CA121947 · NCI · UNIVERSITY OF CALIFORNIA LOS ANGELES · PI MITSUYASU, RONALD T. · 2006 to 2014
$54.7M
ROLE OF Rac AND REACTIVE OXYGEN SPECIES IN KAPOSI'S SARCOMA VIRAL ONCOGENESISR01CA136387 · NCI · UNIVERSITY OF MIAMI SCHOOL OF MEDICINE · PI SHEMBADE, NOULA DATTU · 2010 to 2024
$7.1M
(PQ 6) New Models of KSHV Oncogenesis and KS Immune EnvironmentR01CA250074 · NCI · WEILL MEDICAL COLL OF CORNELL UNIV · PI CESARMAN, ETHEL · 2020 to 2024
$2.8M
The Nucleolar Detention Center: a Hub of Long Noncoding RNAs that Imprison Proteins During StressR01GM115342 · NIGMS · UNIVERSITY OF MIAMI SCHOOL OF MEDICINE · PI LEE, STEPHEN · 2015 to 2022
$2.6M
Induction of Tumor Cell Dormancy by Ribosomal Intergenic Spacer Noncoding RNAR01CA200676 · NCI · UNIVERSITY OF MIAMI SCHOOL OF MEDICINE · PI LEE, STEPHEN · 2016 to 2020
$1.7M
NCI NIH HHS R01 CA136387NCI NIH HHS R01 CA200676NCI NIH HHS R01 CA250074NCI NIH HHS U01 CA121947NIAID NIH HHS UM1 AI068634NIAID NIH HHS UM1 AI068636NIAID NIH HHS UM1 AI106701NIGMS NIH HHS R01 GM115342
6 · The paper itself

Abstract

Kaposi's sarcoma herpesvirus (KSHV) is an angiogenesis-inducing oncovirus whose ability to usurp the oxygen-sensing machinery is central to its oncogenicity. By upregulating the hypoxia-inducible factors (HIFs), KSHV reprograms infected cells to a hypoxia-like state, triggering angiogenesis. Here we identify a link between KSHV replicative biology and oncogenicity by showing that KSHV's ability to regulate HIF2α levels and localization to the endoplasmic reticulum (ER) in normoxia enables translation of viral lytic mRNAs through the HIF2α-regulated eIF4E2 translation-initiation complex. This mechanism of translation in infected cells is critical for lytic protein synthesis and contributes to KSHV-induced PDGFRA activation and VEGF secretion. Thus, KSHV regulation of the oxygen-sensing machinery allows virally infected cells to initiate translation via the mTOR-dependent eIF4E1 or the HIF2α-dependent, mTOR-independent, eIF4E2. This "translation initiation plasticity" (TRIP) is an oncoviral strategy used to optimize viral protein expression that links molecular strategies of viral replication to angiogenicity and oncogenesis.

Indexed as

Peptide Chain Initiation, TranslationalVirus ReplicationBasic Helix-Loop-Helix ProteinsCarcinogenesisEndothelial PAS Domain-Containing Protein 1Eukaryotic Initiation Factor-4EHerpesvirus 8, HumanHumansHypoxiaSarcoma, KaposiVirus ActivationBasic Helix-Loop-Helix ProteinsEIF4E2 protein, humanEndothelial PAS Domain-Containing Protein 1Eukaryotic Initiation Factor-4EeIF4E2 cap bindingEPAS1HHV-8hypoxia-inducible factorsKaposi’s sarcoma herpesvirusKSHVoxygen-regulated translation initiationPDGFRAviral oncogenesisviral replication

Identifiers

PMID34965440
PMCPMC9121799
OpenAlexW4200614149

What OpenQuestion holds

Textmetadata
LicenceCC BY-NC-ND
Read underepoch 390

Registered trials

None linked

Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.